Evolution Of Protein Kinases

It is clear protein serine/threonine kinases and protein tyrosine kinases play a major role in eukaryotic signal transduction pathways. Despite this, there are no such kinases in prokaryotes, as these only contain histidine kinases. So where do they come from? One possibility is that protein kinases evolved from bacterial defense enzymes that confer antibiotic resistance. This possibility was noted when the crystal structure of a bacterial aminoglycoside antibiotic metabolizing enzyme was solved. Surprisingly, this enzyme had a three-dimensional fold very similar to eukaryotic protein kinases. In addition, this enzyme has a very similar reaction mechanism to protein kinases, in that it transfers the y-phosphate group from ATP to hydroxyls in the antibiotic. Interestingly, bacterial aminoglycoside kinases can be inhibited with some protein kinase inhibitors that act as competitive ATP antagonists. Therefore, there is a possibility that the study of protein kinases may contribute to solving a seemingly unrelated problem—the increasing resistance of bacteria to clinically used antibiotics.

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